Figure 1.
Immunoblotting analysis of mitochondrial dynamics and biogenesis proteins. (A) Shows representative immunoblotting analysis of 6-month-old WT, Drp1+/−, APP and APPXDrp1+/− mice. (B) Shows quantitative densitometry analysis of mitochondrial dynamics proteins Drp1, Fis1, Mfn1, Mfn2, Opa1 and a matrix protein, CypD. (C) Shows quantitative densitometry analysis of mitochondrial biogenesis proteins PGC1α, Nrf1, Nrf1, and TFAM. The fission proteins Drp1 (P = 0.001) and Fis1 (P = 0.002) and matrix protein CypD (P = 0.01) were significantly increased; and the fusion proteins Mfn1 (P = 0.01), Mfn2 (P = 0.01), and Opa1 (P = 0.03) were significantly decreased in APP mice relative to WT mice, indicating the presence of abnormal mitochondrial dynamics. On the contrary, in APPXDrp1+/− mice relative to APP mice, the fission proteins Drp1 (P = 0.01) and Fis1 (P = 0.03) and matrix protein CypD (P = 0.01) were significantly decreased; and the fusion proteins Mfn1 (P = 0.04), Mfn2 (P = 0.01), and Opa1 (P = 0.04) were significantly increased, indicating that reduced Drp1 protects against mutant APP and Aβ-induced mitochondrial dynamics toxicity. The levels of mitochondrial biogenesis proteins PGC1α (P = 0.01), Nrf1 (P = 0.01), Nrf2 (P = 0.004) and TFAM (P = 0.001) were significantly decreased in APP mice relative to WT mice. In APPXDrp1+/− mice relative APP mice, biogenesis proteins PGC1α (P = 0.01), Nrf1 (P = 0.01), Nrf2 (P = 0.01) and TFAM (P = 0.01).

